The implantation of stents has become established as one of the most effective therapeutic measures in the treatment of vascular diseases. The purpose of stents is to assume a supporting function in hollow organs in a patient. Stents of a traditional design therefore have a tubular basic body with a filigree supporting structure of metallic struts, which is present initially in a compressed form for introduction into the body and then is widened at the site of application. One of the main areas of application of such stents is for permanent or temporary widening of vascular stenoses and maintaining their patency, in particular for widening occlusions (stenoses) in the coronary vessels. In addition, there are also known aneurysm stents which serve to support damaged vascular walls.
The basic body of the stent consists of an implant material. An implant material is a nonviable material, which is used for an application in medicine and enters into an interaction with biological systems. The basic prerequisites for use of a material as an implant material which comes in contact with the environment of the body when used as intended is its biocompatibility. Biocompatibility is understood to be the ability of a material to induce an appropriate tissue reaction in a specific application. This includes adaptation of the chemical, physical, biological and morphological surface properties of an implant to the recipient tissue with the goal of a clinically desired interaction. The biocompatibility of the implant material also depends on the chronological course of the reaction of the biosystem in which it is implanted. Thus relatively short-term irritation and inflammation occur and may lead to tissue changes. Biological systems thus react in various ways as a function of the properties of the implant material. Implant materials may be subdivided into bioactive, bioinert and degradable/absorbable materials, depending on the reaction of the biosystem.
A biological reaction to implant materials depends on the concentration, the duration of action and how it is supplied. The presence of an implant material alone often leads to inflammation reactions that may be triggered by mechanical stimuli, chemical substances as well as metabolic products. The inflammation process is usually accompanied by migration of neutrophilic granulocytes and monocytes through the vascular walls, migration of lymphocyte effecter cells with the formation of specific antibodies to the inflammation stimulus, activation of the complement system with the release of complement factors, which act as mediators, and ultimately the activation of blood coagulation. An immunological reaction is usually closely associated with an inflammation reaction and may lead to sensitization and the development of an allergy. An essential problem with implantation of stents in blood vessels is in-stent restenosis due to an overshooting neointimal growth, which is caused by a marked proliferation of arterial smooth muscle cells and a chronic inflammatory reaction.
One promising approach toward solving the problem is to use biocorrodible metals and their alloys as an implant material because a permanent supporting function of the stent is not usually necessary. The body tissue, which is initially damaged, regenerates. For example, DE 197 31 021 A1 proposes that medicinal implants should be made of a metallic material, the main components of which are iron, zinc or aluminum and/or an element from the group of alkali metals or alkaline earth metals. Alloys based on magnesium, iron and zinc are described as being especially suitable. Secondary components of the alloys may be manganese, cobalt, nickel, chromium, copper, cadmium, lead, tin, thorium, zirconium, silver, gold, palladium, platinum, silicon, calcium, lithium, aluminum, zinc and iron. In addition, DE 102 53 634 A1 describes the use of a biocorrodible magnesium alloy containing >90% magnesium, 3.7-5.5% yttrium, 1.5-4.4% rare earth metals and <1% remainder, this alloy being suitable in particular for production of an endoprosthesis, e.g., in the form of a self-expanding or balloon-expandable stent. The use of biocorrodible metallic materials in implants should lead to a definite reduction in rejection reactions or inflammation reactions.
It is also known that a higher measure of biocompatibility and thus an improvement in the restenosis rate can be achieved if implant materials are provided with coatings of tissue-compatible materials in particular. These materials are usually of an organic or synthetic polymer nature and in some cases are of natural origin.
If biocorrodible polymers are used the implant material or as the coating material, it should be noted that the products of degradation of these polymers, which are often acidic, can lead to an inflammatory reaction in the surrounding tissue, i.e., the material has only a moderate biocompatibility. For example, it has been proven that with biodegradable poly(ortho esters), neither the monomers nor the intermediate products during degradation are responsible for the inflammation but instead the acetic acid released in traces is responsible (Zignani et al., Subconjunctival biocompatibility of a viscous bioerodible poly(ortho ester), J. Biomed. Water. Res., 1997, 39 pp. 277-285). In addition to the unwanted biological response to the acidic degradation products, the altered pH in the case of an implant of a biocorrodible magnesium alloy with a coating of such a polymer also influences the degradation properties of the alloy: the acidic environment accelerates the degradation. Therefore, a stent made of a biocorrodible magnesium alloy, for example, loses its supporting power more rapidly.
According to another strategy for preventing restenosis, proliferation is to be inhibited by medication. Drug-coated stents (also known as DES. i.e., drug-eluting stents) in which the drugs have been proven to suppress the proliferation of smooth human vascular muscle cells are also known; examples include the drugs sirolimus and paclitaxel. One disadvantage is the concomitant medication required to prevent a late thrombosis, the high cost of the drugs used so far for the purpose of prevention of a restenosis as well as their complex processing.